Nonmuscle cells have almost ubiquitously evolved a mechanism to detect and prevent Ca(2+) store depletionstore operated calcium entry. No such mechanism has, as yet, been reported in cardiac myocytes. However, it is conceivable that such a mechanism may play an important role in cardiac Ca(2+) homeostasis to ensure the availability of sufficient stored Ca(2+) to maintain normal excitation contraction coupling. We present data that confirms the presence of a mechanism that is able to monitor the Ca(2+) load of the SR and initiate a signaling process to accelerate Ca(2+) uptake by the SR when store depletion is detected. Depletion of SR Ca(2+) activates a protein kinase, the principal SR substrate of which is phospholamban. Phosphorylation of this SR protein promotes Ca(2+) pump activity and therefore store refilling. Furthermore, a protein kinase activity associated with the SR that is inhibited by Ca(2+) ions has been identified. We have measured lumenal [Ca(2+)] by using a fluorescent Ca(2+) indicator and found that by initiating Ca(2+) uptake and increasing Ca(2+) load, we can inhibit the protein kinase activity associated with the SR. This confirms that a protein kinase, that is regulated by lumenal [Ca(2+)], has been identified and represents part of a previously unidentified signalling cascade. This local feedback mechanism would allow the myocyte to detect and prevent SR Ca(2+) load depletio
To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.